Background/Purpose: RA patients (pts) are at increased risk of herpes zoster (HZ), and ACR guidelines recommend vaccination in pts aged ≥50 years prior to starting biologic DMARDs or tofacitinib.¹ Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Live zoster vaccine (LZV) has shown 70% efficacy in immunocompetent adults aged 50–59 years, and 51% efficacy in those aged ­≥60 years.² We previously reported that RA pts on background methotrexate who started 3 months of treatment with tofacitinib after LZV had similar varicella zoster virus (VZV)-specific immunity to placebo (PBO) pts, and that their VZV immunity at Week (Wk) 6 post-vaccination was comparable with healthy individuals aged ≥50 years.³ The objective of this study was to evaluate the long-term effectiveness of LZV in pts with RA, via the incidence of HZ after treatment with tofacitinib for up to 27 months.

Methods: The initial study involved 112 RA pts given LZV and randomized 2–3 wks later to tofacitinib 5 mg twice daily (BID) or PBO for 12 wks (A3921237 [NCT02147587]). At 14 wks post-vaccination, pts joining the long-term extension ORAL Sequel study (NCT00413699) initiated open-label treatment with tofacitinib 5 or 10 mg BID. The incidence of post-vaccination HZ after tofacitinib exposure up to 27 months (based on an extended follow-up beyond the January 2016 data snapshot) was evaluated. Among HZ cases, we analyzed measures of VZV-specific immunity with average immunity after LZV.

Results: 112 pts were randomized to PBO (n=57) or tofacitinib 5 mg BID (n=55). 100 pts continued to receive tofacitinib in ORAL Sequel. Five cases (not adjudicated) of HZ occurred, with an incidence rate (pts with events per 100 pt-years) of 3.60 (95% confidence interval 1.17, 8.39) (#1: 202 days [219 days post-LZV], #2: 267 days [281], #3: 702 days [748], #4: 699 days [741], #5: 446 days [544] after initiation of tofacitinib). Cases #1–#4 were monodermatomal; case #5 involved 5 dermatomes. All cases resolved with treatment. Cases #1, #4, and #5 had undetectable ELISPOT measures at baseline and at Wk 6 post-vaccination, indicating a lack of VZV-specific immunity. Cases #2 and #3 responded adequately to vaccination by both immunoglobulin G (IgG) and ELISPOT measures, but had lower-than-average VZV IgG levels, both at baseline and at Wk 6 (Table).

Conclusion: LZV prior to treatment with tofacitinib is effective at boosting IgG levels and cell-mediated immunity towards VZV. Of the 5 pts who developed HZ, 3 did not have any measurable cell-mediated response, and 2 had a low humoral response.

References: 1. Singh JA et al. Arthritis Care Res (Hoboken) 2016;68:1-25.

2. Hales CM et al. MMWR Morb Mortal Wkly Rep 2014;63:729-31.

3. Winthrop K et al. Arthritis Rheumatol 2015;67:Abstract 12L.

Acknowledgment: The authors would like to acknowledge Lisa McNeil.